Benzohydrazide and Phenylacetamide Scaffolds: New Putative ParE Inhibitors
| العنوان: | Benzohydrazide and Phenylacetamide Scaffolds: New Putative ParE Inhibitors |
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| المؤلفون: | Afzal Azam Mohammed, Ashish Wadhwani, Bharat Kumar Reddy Sanapalli, Vidyasrilekha Yele |
| المصدر: | Frontiers in Bioengineering and Biotechnology Frontiers in Bioengineering and Biotechnology, Vol 9 (2021) |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Histology, Biomedical Engineering, Bioengineering, medicine.disease_cause, DNA gyrase, 03 medical and health sciences, 0302 clinical medicine, antibacterial activity, medicine, antibiofilm activity, 030212 general & internal medicine, ParE, Escherichia coli, IC50, 030304 developmental biology, Original Research, chemistry.chemical_classification, 0303 health sciences, biology, Chemistry, Bioengineering and Biotechnology, biology.organism_classification, phenylacetamide derivatives, Ciprofloxacin, Enzyme, Biochemistry, Gentamicin, Antibacterial activity, benzohydrazide derivatives, Bacteria, TP248.13-248.65, medicine.drug, Biotechnology |
| الوصف: | Antibacterial resistance (ABR) is a major life-threatening problem worldwide. Rampant dissemination of ABR always exemplified the need for the discovery of novel compounds. However, to circumvent the disease, a molecular target is required, which will lead to the death of the bacteria when acted upon by a compound. One group of enzymes that have proved to be an effective target for druggable candidates is bacterial DNA topoisomerases (DNA gyrase and ParE). In our present work, phenylacetamide and benzohydrazides derivatives were screened for their antibacterial activity against a selected panel of pathogens. The tested compounds displayed significant antibacterial activity with MIC values ranging from 0.64 to 5.65 μg/mL. Amongst 29 title compounds, compounds 5 and 21 exhibited more potent and selective inhibitory activity againstEscherichia coliwith MIC values at 0.64 and 0.67 μg/mL, respectively, and MBC at onefold MIC. Furthermore, compounds exhibited a post-antibiotic effect of 2 h at 1× MIC in comparison to ciprofloxacin and gentamicin. These compounds also demonstrated the concentration-dependent bactericidal activity againstE. coliand synergized with FDA-approved drugs. The compounds are screened for their enzyme inhibitory activity againstE. coliParE, whose IC50values range from 0.27 to 2.80 μg/mL. Gratifyingly, compounds, namely 8 and 25 belonging to the phenylacetamide series, were found to inhibit ParE enzyme with IC50values of 0.27 and 0.28 μg/mL, respectively. In addition, compounds were benign to Vero cells and displayed a promising selectivity index (169.0629–951.7240). Moreover, compounds 1, 7, 8, 21, 24, and 25 (IC50: 200) exhibited potent activity in reducing theE. colibiofilm in comparison with ciprofloxacin, erythromycin, and ampicillin. These astonishing results suggest the potential utilization of phenylacetamide and benzohydrazides derivatives as promising ParE inhibitors for treating bacterial infections. |
| اللغة: | English |
| تدمد: | 2296-4185 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95aa4b64ee7fd7b2b0d86a4b8642c70cTest http://europepmc.org/articles/PMC8247773Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....95aa4b64ee7fd7b2b0d86a4b8642c70c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22964185 |
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